Herbal medicinal tablet formulation for treating obesity which can be prescribed based on sasang constitutional medicine

ABSTRACT

an ephedra powder agent of which ephedrine content is concentrated to be 3.0 to 4.0%, which is greater than 0.5 to 2.5% when it is in a natural state, and of which the ephedrine content is maintained constant at 3.0 to 4.0%; and a side-effect-preventing powder agent for each constitution prescribed based on Sasang constitutional medicine in order to prevent a side effect of the ephedra powder agent, wherein a weight ratio of the ephedra powder agent and the side-effect-preventing powder agent is 8-10:1 to 9-11:1.

TECHNICAL FIELD Background Art (a) Field of the Invention

The present invention relates to an herbal medicinal tablet formulationfor treating obesity which can be prescribed based on Sasangconstitutional medicine, and more particularly, to an herbal medicinaltablet formulation for treating obesity and being able to be prescribedbased on Sasang Medicine (hereinafter also referred to as “Gambijeong”)that may confirm clinical effectiveness of weight loss while using thesame amount of medicine as a desired prescription, may maintain safetyof the herbal medicine by quantifying an index component for the firsttime among components of diet herbal medicines and controlling anabnormal reaction to the medicine, may maintain a stable treatment ratefor each individual treatment and body weight/obesity by preparing amedicine by a quantitative and standardized method consideringconstitution and weight/obesity based on Sasang constitutional medicine,and may solve problems of a typical oriental medicine diet, such as apeculiar smell or bitter taste of oriental medicine, and inconvenienceof taking such as an excessive dose.

(b) Description of the Related Art

Ephedra sinica Stapf (ephedra) is a perennial shrub of the ephedrafamily of which the grass stem is dried and is medicinal, and is amedicine that has been mainly used in Korean medicine for fever, chroniccough, asthma, and edema.

A main component of ephedra is composed of alkaloids such asL-ephedrine, pseudoephedrine, norephedrine, and norpseudoephedrine, andof these, ephedrine is the largest component at 30 to 90% of totalalkaloids.

Ephedrine has a sympathetic nervous system excitatory effect thatsuppresses appetite, increases heat and metabolism, inhibits cholesterolabsorption in the small intestine, and accelerates body fat breakdown byincreasing energy consumption in adipose tissue.

Due to ephedrine's sympathetic nervous system excitatory effect, Ephedrasinica Stapf is associated with causing cardiovascular, autonomicnervous system, and digestive system symptoms such as headache,tachycardia, elevated blood pressure, and nausea, and thus, it isforbidden to be used as a food in Korea, like in the United States, andis used only as a medicine under a professional prescription of anoriental medicine doctor.

Due to safety concerns due to a side effects of the Ephedra sinicaStapf, use of the Ephedra sinica Stapf in Korea and its capacity issueshave been raised both inside and outside the oriental medicine field,thus, in 2007, the society of Korean medicine for obesity research hasdeveloped clinical practice guidelines for use of Ephedra sinica Stapffor treatment of obesity and weight loss.

However, only a maximum allowable daily dose of ephedrine has beendescribed, and there is a lack of usefulness in actual clinical practicebecause specific and clear criteria are not presented.

A total alkaloid content in ephedra is 0.5 to 2.5%, and the KoreanPharmacopoeia stipulates that the total alkaloid (ephedrine and causticephedrine) content in ephedra should be at least 0.7%.

However, a content of ephedrine in total alkaloids of ephedra variesfrom 30 to 90% depending on the harvesting time and growth environment,and when comparing an ephedrine extraction amount at a time of ephedradecoction, since the amount of ephedrine in a control decoction solutioncontaining ephedra corresponds to 73 to 96% of the ephedra's soledecoction solution, an actual ephedrine content varies considerablydepending on a country of origin of a medicinal material, a formulation,a decocting process, or a condition of absorption distribution, and forthis reason, since a blood concentration of a patient may vary, bothstability of a medicine and safety of treatment act as a considerablyunstable factors.

Generally, in the oriental constitutional medicine, the constitution isclassified according to strength and weakness of organs, and especiallyin a case of Taeeumin, Soeumin, and Soyangin, constitutionalphysiological characteristics significantly affect obesity. SinceTaeeumin have a large liver and small lungs, they have strong nutrientabsorption and is easy for them to gain weight, while their ability todissipate and discharge heat and waste products is poor; since Soeuminhave large kidneys and a small spleen, their digestive absorption isweak, and their muscle mass is insufficient, resulting in poormetabolism; and since Soyangin have a large spleen and small kidneys,they have severe stress binge eating and poor detoxification andexcretion functions, so they need a prescription for obesity whileconsidering their constitution. Pathophysiological characteristics ofobesity according to specific constitution are as follows.

According to the characteristics of obesity of Taeeumin, compared toother constitutions, Taeeumin have vigorous digestive function andintestinal absorption, and their average BMI is highest among theconstitutions, and their moderate or high obesity rates are highest.Taeeumin experience large body weight changes, severe swelling, and havea lot of visceral fat, as well as fat in the sides, buttocks, andthighs; their waist-hip ratio (WHR) is high, and metabolic circulationis lowered, so adult diseases such as hypertension, paralysis,hyperlipidemia, and fatty liver are often accompanied; and Taeeumin havea good and large liver, have void and small lungs, and have a wetconstitution, and the skin, lungs, and respiratory organs are weak, soatrophy, allergic dermatitis, rhinitis, bronchial asthma, and hives arelikely to occur.

In addition, according to the obesity characteristics of Soeumin, theyhave weak gastrointestinal function compared to other constitutions, anddigestive disorders are easily generated due to poor intestinalmotility; they often have constipation or diarrhea, and their averageBMI among the constitutions is the lowest; and Korean-style obesity(thin obesity) often occurs due to lack of exercise and lack of musclemass due to poor metabolism. Therefore, there is a large decrease inbasal metabolism due to the lack of muscle mass, and there are a largenumber of weakness-type constitutions that suffer from chronic fatiguedue to weak physical strength and sensitivity. The decrease in metabolicfunction due to low muscle mass generally occurs in the constitutionthat suffers from the most side effects (low blood sugar symptoms suchas dizziness and fatigue) when dieting, and Soeumin constitutionallylack energy so blood circulation falls and the hands and feet are cold,and further, they are sensitive to cold. In this body type, the upperbody is poor and looks dwarfed overall, the abdomen and thigh lower bodyobesity are relatively high, and they suffer a lot from lower bodyedema.

According to the characteristics of obesity of Soyangin, they have agood and large spleen, and void and small kidneys, and they have arepresentative fever constitution and good digestive powers, but havepoor control over stress, which may lead to stressful binge eating,gastritis caused by binge drinking, and digestive problems. In case offrequent drinking or frequent night eating, it is easy to be exposed todiseases such as reflux esophagitis and gastric ulcers. Digestion isgood, but excretion is poor, so probability of constipation is higherthan for other constitutions. Body fat is mainly concentrated in theupper body, and the lower body is poor, which may cause degenerativediseases of the lumbar spine and degenerative knee arthritis due toobesity. The upper body is strong, the lower body is slim, and there aremany body types with the abdomen expanded in the forward direction.

On the other hand, it is a great advantage and feature that the herbalmedicine formulation is prepared with various mixing ratios according torespective medicines and a degree of disease and a constitution of apatient, even for the same disease, however most herbal medicineformulations are used as a propellant, a pill, a powder, a granuleformulation, a concentrated liquid formulation, and a distillate, so theyield of an extract is not constant and it is difficult to confirmclinical effectiveness; in addition, it is uncomfortable to eat with apeculiar herbal odor or bitter taste after taking it and an excessiveamount thereof, and further, it is inconvenient to store, so diet herbalmedicine formulations are not easily used.

DISCLOSURE Technical Problem

The present invention has been made in an effort to provide an herbalmedicinal tablet formulation for treating obesity which can beprescribed based on Sasang constitutional medicine, and moreparticularly, to an herbal medicinal tablet formulation for treatingobesity being able to prescribed based on Sasang Medicine (hereinafteralso referred to as “Gambijeong”) that may confirm clinicaleffectiveness of weight loss while using the same amount of medicine asa desired prescription, may maintain safety of the herbal medicine byquantifying an index component for the first time among components ofdiet herbal medicines and controlling an abnormal reaction of themedicine, may maintain a stable treatment rate for each individualtreatment and body weight/obesity by preparing a medicine by aquantitative and standardized method considering constitution andweight/obesity based on Sasang constitutional medicine, and may solveproblems of a typical oriental medicine diet, such as a peculiar smellor bitter taste of oriental medicine, and inconvenience of taking itsuch as an excessive dose.

Technical Solution

An embodiment of the present invention provides an herbal medicinaltablet formulation for treating obesity which can be prescribed based onSasang constitutional medicine, including:

an ephedra powder agent of which ephedrine content is concentrated to be3.0 to 4.0%, which is greater than 0.5 to 2.5% when it is in a naturalstate, and of which the ephedrine content is maintained constant at 3.0to 4.0%; and a side-effect-preventing powder agent for each constitutionprescribed based on Sasang constitutional medicine in order to prevent aside effect of the ephedra powder agent, wherein a weight ratio of theephedra powder agent and the side-effect-preventing powder agent is8-10:1 to 9-11:1.

Advantageous Effects

According to the embodiment of the present invention, it is possible toprovide an herbal medicinal tablet formulation for treating obesitybeing able to prescribed based on Sasang Medicine that may confirmclinical effectiveness of weight loss; that may maintain safety of theherbal medicine by quantifying the index component among the componentsof a diet herbal medicine and controlling an abnormal reaction of themedicine regardless of the collection time, growth environment, mixture,or conditions of a decocting process or absorption distribution; thatmay shorten a treatment period within less than 3 months compared toother western medicine or oriental medicines; that may maintainpersonalized treatment and a stable treatment rate for eachweight/obesity by quantified and standardized usage consideringconstitution, weight, and obesity according to Sasang constitutionalmedicine; and that may solve the problems of the traditional orientalmedicine diet, such as the peculiar smell, bitterness, excessive doses,and discomfort of taking of the traditional oriental medicine.

DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a photograph of an herbal medicinal tabletformulation for treating obesity which can be prescribed based on Sasangconstitutional medicine according to an embodiment of the presentinvention.

FIG. 2 illustrates a graph analyzing a weight loss ratio after 3 monthsof taking an herbal medicinal tablet formulation for treating obesitywhich can be prescribed based on Sasang constitutional medicineaccording to an embodiment of the present invention.

FIG. 3 illustrates a graph analyzing a change in body fat mass after 3months of taking an herbal medicinal tablet formulation for treatingobesity which can be prescribed based on Sasang constitutional medicineaccording to an embodiment of the present invention.

FIG. 4 illustrates a graph analyzing a lipase inhibitory ability test ofan herbal medicinal tablet formulation for treating obesity which can beprescribed based on Sasang constitutional medicine according to anembodiment of the present invention.

FIG. 5 illustrates a flowchart of a manufacturing method of an ephedrapowder agent for an herbal medicinal tablet formulation for treatingobesity which can be prescribed based on Sasang constitutional medicineaccording to an embodiment of the present invention, and aside-effect-preventing powder agent, by constitution.

FIG. 6 illustrates a flowchart of a manufacturing method of an herbalmedicinal tablet formulation for treating obesity which can beprescribed based on Sasang constitutional medicine according to anembodiment of the present invention.

FIG. 7 to FIG. 9 respectively illustrate graphs for measuring anephedrine content every 2 hours for 10 lots in a decocting process for 4different ephedra with different producing districts and collectingperiods so as to manufacture an ephedra powder agent for an herbalmedicinal tablet formulation for treating obesity which can beprescribed based on Sasang constitutional medicine according to anembodiment of the present invention.

FIG. 10 and FIG. 11 respectively illustrate graph for explaining apattern relationship between a Brix content and an ephedrine content inmanufacturing an ephedra powder agent for an herbal medicinal tabletformulation for treating obesity which can be prescribed based on Sasangconstitutional medicine according to an embodiment of the presentinvention, by using the results shown in FIG. 7 to FIG. 9.

MODE FOR INVENTION

Hereinafter, the present invention will be described more fully withreference to the accompanying drawings, in which exemplary embodimentsof the invention are shown. As those skilled in the art would realize,the described embodiments may be modified in various different ways, allwithout departing from the spirit or scope of the present invention.Accordingly, the drawings and description are to be regarded asillustrative in nature and not restrictive. Like reference numeralsdesignate like elements throughout the specification.

In the present specification, unless explicitly described to thecontrary, the word “comprise” and variations such as “comprises” or“comprising” will be understood to imply the inclusion of statedelements but not the exclusion of any other elements.

First, as shown in FIG. 1, an herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine according to an embodiment of the present invention has thesame hardness as a typical tablet formulation; is quickly disintegratedwithout burdening the stomach when taken with water; has a size of5.00±30 mm, which is about half the size of a typical tabletformulation, while it has a rectangular shape so that the neck does notfeel pain when taking it due to characteristics of an herbal medicinewith a large or rough surface; and has a disintegration time within 30minutes and hardness of about 12.0 kp.

The following Experimental Example 1 was performed on 100 patients whovisited the oriental medical clinic of the present applicant in order toconfigure the herbal medicinal tablet formulation for treating obesitywhich can be prescribed based on Sasang constitutional medicineaccording to the embodiment of the present invention described above.

Experimental Example 1

In order to configure the herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine according to the embodiment of the present invention describedabove, commercially available round, rectangular, triangular, and squaretablet formulation shapes; tablet formulations of a typical size, ½size, and less than ½ size; disintegration times of 20 minutes, 30minutes, 40 minutes, and a hour; a degree of smearing on the hand; andpreference of hardness were determined as very good, good, normal, andbad, and are shown in Table 1.

Table 1 shows the results of investigation for the size, thedisintegration degree, the degree of smearing on the hand, and thepreference of hardness of the herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine according to the embodiment of the present invention

TABLE 1 Very good Good Normal Bad Shape Rectangle Rectangle Rectangle 42people 7 17 34 prefer different shapes Size ½ general ½ general ½general 30 people size size size prefer 20 31 19 about general size orabout half or less the general size Disintegration Within 30 Within 30Within 30 Prefer minutes minutes minutes within 20 18 23 29 minutesDegree of Degree of Degree of not Degree of not smearing not being beingbeing on hand smeared on smeared on smeared on and hands and hands andnot hands and not hardness not easily easily easily broken 17 broken 24broken 27

As shown in Table 1, it was found that 58 out of 100 ordinary people hada preference of ‘Normal’ or more for the rectangular shape; that as forthe size, 70 people had a preference of ‘Normal’ or more for about ½ orless than the typical size; that as for the load hardness and the degreeof disintegration, 68 people preferred the same hardness as that of thetypical tablet formulation and the degree of disintegration that was notsmeared on hand and was easily broken; and that 70 people preferred itto disintegrate in water within 30 minutes.

As a result, the herbal medicinal tablet formulation for treatingobesity which can be prescribed based on Sasang constitutional medicineaccording to the embodiment of the present invention was a rectangulartablet formulation and could be prescribed to be stored in a plasticcontainers for one month; it could be taken with water after meals; itwas an herbal medicine, but there was no concern about deteriorationwhen exposed to air, and it was not bulky; and it could solve theproblems that may occur when taking common herbal medicines by rapiddisintegration, without problems such as smearing when picking up byhand or the peculiar smell or difficult swallowing of typical herbalmedicines.

On the other hand, the herbal medicinal tablet formulation for treatingobesity which can be prescribed based on Sasang constitutional medicineaccording to the embodiment of the present invention increased theephedrine content, which was the target substance (active ingredient)that provided the effect of reducing obesity, to 3.0-4.0% compared to0.5 to 2.5% that was the content of natural ephedra; it included theephedra powder agent that achieves medicinal effect stability bymaintaining the constant ephedrine content, the side-effect-preventingpowder agent for each constitution prescribed by taking intoconsideration the characteristics of Sasang constitutional medicineconstitution, that is, Soeumin, Taeeumin, Soyangin, and Taeyangin inorder to alleviate the side effect of the ephedra powder agent, and thedisintegrant to provide the hardness and disintegration timecorresponding to that of the typical tablet formulation; and the weightratio of the ephedra powder agent and the side-effect-preventing powderagent for each constitution (hereinafter also referred to as “Gambisan”)was 8-10:1 to 9-11:1.

According to a paper published in September of 2017 in the Journal ofKorean Medicine [A Study on the Effectiveness and Stability of Ephedraand Ephedrine in the Treatment of Obesity-Focused on RCT Research], theephedra and ephedrine-administered groups showed weight and body fatloss when compared to the control group when taken for 20 weeks or more.According to a paper published in 2000 in the International Journal ofObesity, “Safety and efficacy of treatment with an ephedrine/caffeinemixture. The first double-blind placebo-controlled pilot study inadolescents.”, compared to the control group, it was found that thecombination of ephedrine and caffeine showed a significant weight losseffect; and according to a paper published in 2013 in the internationaljournal “Obesity”, “The Effect of Leptin, Caffeine/Ephedrine and theirCombination Upon Visceral Fat Mass and Weight Loss.”, during the 25-weekstudy period, the combination formulation containing ephedrine showed asignificant weight loss effect compared to the leptin alone formulation,and in most cases, there was the inconvenience of maintaining theprescription for about 6 months.

The herbal medicinal tablet formulation for treating obesity which canbe prescribed based on Sasang constitutional medicine according to theembodiment of the present invention may be approved by the U.S. FDA upto pseudoephedrine at 240 mg/day, and ephedrine at 150 mg/day for OTCmedicine; in the treatment of obese patients, when 5% of the initialweight is lost within 3 months, the effectiveness of the medicine isrecognized, and when 10% thereof is lost, successful weight loss isrecognized; and particularly, since 5-10% of weight loss may improveobesity-related diseases and reduce complications, the clinical practiceguidelines from the Korean Society for Obesity make it possible toachieve an effective obesity reduction effect within 3 months within therange of 150 mg/day, the US FDA-allowed ephedrine content, consideringthat the goal of weight loss in obese patients is to target 5-10% oftheir initial weight loss over the course of 3-6 months.

In addition, with respect to the herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine according to the embodiment of the present invention, thelipase activity experiment of Experimental Example 4 below wasperformed, and it was confirmed that the lipase activity was inhibitedas the ephedrine content increased; and through Experimental Example 2,while effective ephedrine content within the range of 150 mg/day, whichis the US FDA-allowed ephedrine content, achieved effective weight losswithin 3 months for each constitution classified as Soeumin, Soyangin,Taeeumin, and Taeyangin, it was possible to determine the weight ratioof the appropriate ephedra powder and side-effect-preventing powderagent for each constitution with few side effects.

First, the prescription of side-effect-preventing powder agent for eachconstitution to eliminate each constitutional side effect of ephedraaccording to Sasang constitutional medicine is as follows.

As shown in Table 2 below, the prescription for theside-effect-preventing powder agent for each constitution was based onthe ephedra weight of 1, and had the pharmacological effect supplementedby considering the side effects that occur during diet by constitution,wherein the prescription included medicinal content confirmed throughlong-term clinical experience, the Sasang Constitutional Journal, theKorean Oriental Internal Medicine Journal, the Botanical List, theKorean Oriental Medicine Journal, and theses.

Table 2 shows the constitutional side effect of Sasang constitutionalmedicine, the prescription of the side-effect-preventing powder agentfor each constitution for preventing this side effect, and thepharmacological effect of each medicinal content.

TABLE 2 Constitutional Pharmacological Constitutionalside-effect-preventing effect of each side effect powder agent herbTaeeumin Taeeumin prescription Gastrointestinal Occurrence forside-effect- endocrine cell of atopic preventing powder functionregulation dermatitis, agent for each Anti-lipid allergic constitution:alisma 1, effect, antioxidant dermatitis, platycodon 1, effect,rhinitis, puerariae 1, acorus anti-inflammatory effect bronchialgramineus1, semen on asthma, castanea mollissima 2, allergic reactionurticaria, coicis semen Anti-obesity effect etc. due to 2, semen raphani1, weak skin, armeniacae lungs, and amarum 1, cinnamon- respiratory vine2, semen system nelumbinis 2 Soyangin Soyangin prescription Weight loss,Clinically, for side-effect- improved lipid constipation, preventingpowder metabolism, acne, urinary agent for each increased heatinflammation, constitution: talcum 2, metabolism, etc. plaster 1,improved occurrence peppermint 1, constipation, gardeniae fructus 1, andsuppressed fat schizonepeta 1, accumulation rhubarb 1, natrii effectsulfas 1, rehmanniae radix cervi 2, moutan 1 Soeumin prescription Immuneactivity for side-effect- efficacy, Soeumin preventing powder Cellprotective Most frequently agent for each effect against complainedconstitution: oxidative stress, of low blood ginseng radix 1,hypoglycemic sugar astragali radix 2, effect, anti-inflammatory symptomssuch atractylodis effect, as dizziness macrocephalae rhioma 1, treatmentfor atopic and fatigue cinnamon dermatitis, during diet 1, ginger 1,poria analgesic, cocos 1, zizyphi sedative effect, fructus1, hawthorn 1,parasympathetic citrus unshiu effect in the markovich 1, intestine, etc.magnoliae cortex 1

Experimental Example 2 was performed for patients who visited the

Korean clinic of the applicant during the 2017 year and prepared ananalysis report, wherein the maximum amount of ephedrine content withinthe range of the US FDA daily allowable ephedrine content was constantat 2.8 to 3.3%, and the weight ratio of ephedra powder, and the stableweight ratio of the side-effect-preventing powder agent for eachconstitution with respect to the ephedra powder, was different.According to the analysis report of patients who visited the applicant'sclinic in 2017, although the amount of the ephedra powder varieddepending on the time and location of the ephedra, when the ephedrinecontent is constant at 3.0-4.0%, about 360 g was in Taeeumin, about 297g was in Soeumin, and about 360 g was in Soyangin; and when the weightratio of the constitutional stable side-effect-preventing powder agentwith respect to the ephedra powder was 8-10:1 in Taeeumin, 9-11:1 inSoeumin, and 8-10:1 in Soyangin, and when the reduction ratio and sideeffects were analyzed for 278 patients who visited the applicant'sclinic again after taking the composition for each constitution for 3months, as shown in Table 3 and Table 4, it was determined that theephedrine content was 3.0-4.0%, indicating a weight effect within theeffective range for each constitution.

Table 3 shows the results of experiments of the appropriate weight ofephedra powder by Sasang medical constitution.

TABLE 3 Ephedra powder Weight (g) 400 380 360 340 320 300 280 TaeeuminAppeal for Appeal for Appeal for Insufficient Insufficient InsufficientInsufficient weight loss weight loss weight loss weight loss weight lossweight loss weight loss side effect side effect side effect withinwithin within within within within within effective effective effectiveeffective effective effective effective range range range range rangerange range Soeumin Appeal for Appeal for Appeal for Appeal for Appealfor Appeal for Insufficient weight loss weight loss weight loss weightloss weight loss weight loss weight loss side effect side effect sideeffect side effect side effect side effect within within within withinwithin within within effective effective effective effective effectiveeffective effective range range range range range range range SoyanginAppeal for Appeal for Weight loss Insufficient Insufficient InsufficientInsufficient weight loss weight loss within weight loss weight lossweight loss weight loss side effect side effect effective within withinwithin within within within range effective effective effectiveeffective effective effective range range range range range range

According to the results of Table 3, the weight of the ephedra powder,which showed the weight loss effect within the effective range for eachconstitution, was determined when the ephedrine content is constant at3.0 to 4.0%; and for the weight of the ephedra powder, which showedweight loss within the effective range, it was determined whether sideeffects did not appear, while showing weight loss within the effectiverange when the weight of the side-effect-preventing powder agent foreach constitution for constitutional stability varied. Here, even a casein which one of the patients who visited the clinic complained of sideeffects was indicated as the side effect appearance, and the weight losswithin the effective range was the case of weight loss less than 5% whenmeasured after 3 months.

Table 4 shows the weight of the side-effect-preventing powder agent byconstitution, whether or not weight loss by constitution, and whether ornot side effects occurred.

TABLE 4 Constitutional side-effect-preventing powder agent/weight 20 g30 g 40 g 50 g 60 g 70 g 80 g Taeeumin/(Ephedra Complaint of Complaintof Weight loss Insufficient Complaint of Insufficient Complaint ofpowder 360 g) weight loss weight loss within weight loss insufficientweight loss insufficient side effect side effect effective within weightloss within weight loss within within range effective side effecteffective side effect effective effective range within effective rangewithin effective range range range range Soeumin/(Ephedra Complaint ofWeight loss Complaint of Complaint of Complaint of Complaint ofComplaint of powder 300 g) weight loss within weight loss insufficientinsufficient weight loss insufficient side effect effective side effectweight loss weight loss side effect weight loss within range within sideeffect side effect within side effect effective effective within withineffective within range range effective effective range effective rangerange range Soyangin/(Ephedra Complaint of Complaint of Weight lossInsufficient Complaint of Insufficient Complaint of powder 360 g) weightloss weight loss within weight loss insufficient weight lossinsufficient side effect side effect effective within weight loss withinweight loss within within range effective side effect effective sideeffect effective effective Weight loss range within effective rangewithin range range within Insufficient range Insufficient effectiveComplaint of Complaint of effective weight loss Insufficient weight lossrange weight loss weight loss range within weight loss withinInsufficient side effect side effect effective within effectiveeffective weight loss within within range range range within effectiveeffective effective range range range

That is, in the case of Taeeumin, the weight loss within the effectiverange was shown for 360 g of ephedra powder, but it was found that whenthe ratio of the ephedra power and the side-effect-preventing powderagent for each constitution was larger than 8-10:1, there were cases inwhich weight loss was not achieved within the effective range, andpeople complaining of side effects appeared.

In addition, in the case of Soeumin, the weight loss within theeffective range was shown for 300 g of ephedra powder, but it was foundthat when the ratio of the ephedra power and the side-effect-preventingpowder agent for each constitution was larger than 9-11:1, there werecases in which weight loss was not achieved within the effective range,and people complaining of side effects appeared.

In addition, in the case of Soeumin, the weight loss within theeffective range was shown for 300 g of ephedra powder, but it was foundthat when the ratio of the ephedra power and the side-effect-preventingpowder agent for each constitution was larger than 9-11:1, there werecases in which weight loss was not achieved within the effective range,and people complaining of side effects appeared.

Meanwhile, the height, initial weight, body fat mass, and initial musclemass of patients to which Experimental Example 2 was applied and whovisited the Korean clinic of the applicant in 2017 showing the resultsof Table 3 and Table 4, are as follows.

Table 5 is a table summarizing information about the height, initialweight, initial body fat mass, and initial muscle mass of patients whovisited the applicant's clinic in 2017.

TABLE 5 Standard Item Average Deviation Minimum Maximum Height (cm)161.37 6.49 142.00 186.80 Initial weight (kg) 72.23 15.16 50.08 161.64Initial body fat mass (kg) 28.12 8.82 12.60 67.86 Initial muscle mass(kg) 24.01 4.75 17.10 54.7

Therefore, according to the result of analyzing the weight loss ratio of278 people after taking the herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine prescribed by considering the weight ratio of the side effectspreventing powder agent for each constitution with respect to theephedra powder agent as in the result of Experimental Example 2considering each constitution, for 3 months (strictly 10 to 12 weeks),as shown in FIG. 2, the average weight loss was 6.88 kg, and thedifference was statistically significant (p-value=0.000).

Success in losing weight in obesity treatment is defined as losing 5 to10% of weight, and the weight loss ratio of the present composition was9.37% on average, indicating that it was close to successful weight lossin both medical and clinical aspects.

In addition, as shown in Table 6, 243 patients (87.4%) of the 278patients lost 5% or more of their body weight, and 115 patients of 278patients (41.4%) lost 10% or more of their body weight. Therefore, itcan be seen that 87.4% (87 out of 100) of the patients who visitedNubebe Korean medicine clinic may lose 5% or more of their weight.

Table 6 is a table showing the percentage distribution of weight lossamong patients who visited the applicant's clinic.

TABLE 6 Number of Classification patients Percent Weight loss of 243people 87.4% 5% or more Weight loss of 115 people 41.4% 10% or more

As shown in FIG. 3, as a result of comparing the changes in the initialbody fat mass and the body fat mass after 3 months of taking themediation, an average of 5.77 kg was lost and the difference wasstatistically significant (p-value=0.000). In the muscle mass, there wasan average decrease of 0.56 kg, and there was also a statisticallysignificant difference (p-value=0.000). However, the p-value is aprobability value that is affected by a sample size, and tends toapproach 0 as the sample size increases. That is, since data withsufficient or large sample sizes may show significant results even forvery small differences, it is necessary for an analyst to check thestatistical significance and to determine whether there is thesubstantial significance in the difference in results. In the musclemass, a change of about 0.56 kg was observed before and after the actualtreatment, and clinically, the weight loss effect of the presentapplication may be considered to mainly originate from the body fat losseffect. In addition, as shown in Table 7, patients with normal weightlost an average of 7.99% compared to the first treatment, and patientswith high obesity lost an average of 9.89% compared to the firsttreatment. Although the present composition achieved an effective weightloss effect even at the normal weight, it showed a successful weightloss especially in obese patients (including obesity and high obesity).

Table 7 summarizes the percentage of weight loss with respect to theobesity state of patients who visited the applicant's clinic.

TABLE 7 Percentage of Classification weight loss Normal Average weightloss of 7.99% Overweight Average weight loss of 8.02% Obesity Averageweight loss of 9.36% Extreme obesity Average weight loss of 9.89%

In addition, as shown in Table 8, regardless of the degree of obesity,in the analysis by weight band, among the 278 patients, the number ofpatients in the 50 kg band was 39, the number of patients in the 60 kgband was 117, the number of patients in the 70 kg band was 66, and thenumber of patients in the 80 kg band was 26, and the number of patientsin the 90 kg band and the 100 kg or more band respectively was 15,respectively. Table 8 is a table showing weight loss by weightregardless of obesity.

TABLE 8 Standard Average Standard Average deviation weight deviation ofweight of weight loss weight Weight loss loss ratio loss ratio  50 kgband  4.74 kg 1.94 kg  8.33% 3.35%  60 kg band  5.80 kg 2.28 kg  8.93%3.46%  70 kg band  7.67 kg 2.79 kg 10.25% 3.55%  80 kg band  7.75 kg4.05 kg  9.12% 4.77%  90 kg band  9.78 kg 5.26 kg 10.37% 5.52% 100 kgband 12.89 kg 4.84 kg 11.06% 3.88% Total  6.87 kg 3.51 kg  9.37% 3.81%

As shown in Table 8, it can be seen that as the weight increased from 50kg to 100 kg or more, the average weight loss also increased. However,in the average weight loss ratio, it can be seen that the average weightloss ratio of patients of the 70 kg band was 10.25%, which was higherthan the weight loss ratio of patients of the 80 kg band. The minimumand maximum values of the weight loss ratio of the patients of the 70 kgband were 3.27% and 20.96%, respectively, and the minimum and maximumvalues of the weight loss ratio of the patients of the 80 kg band were−0.99% and 18.27%, respectively, wherein the weight loss ratio of somepatients was 0.60%. The average weight loss ratio increased to 9.89%,excluding the patients who gained weight and whose weight loss ratio was0%, among patients of the 80 kg band. Therefore, among the patients ofthe 80 kg band, there was a patient who gained weight, and it can beseen that this had an effect on the average weight loss ratio. Based onclinical data, the weight loss effect of the present composition wasclose to successful weight loss in a medical and clinical sense, andconsidering the time taken, rapid weight loss was achieved in a shortperiod of 10 weeks compared to other medicines (western medicine andherbal medicine).

It can be seen that even in the process of complex preparation, theephedra was extracted alone; the stability of the medicine wasmaintained by quantifying the indicator component; the safety oftreatment was maintained by adjusting the content of the indicatorcomponent in consideration of weight and obesity; and it maintained anexcellent treatment rate and reduced the duration of the dose,consequently improving the treatment rate.

On the other hand, among the compositions of the herbal medicinal tabletformulation for treating obesity which can be prescribed based on Sasangconstitutional medicine according to the embodiment of the presentinvention, in general, in the case of Taeeumin, obesity became asensitive problem, and thus, a lipase inhibitory efficacy test of theherbal medicinal tablet formulation for treating obesity which can beprescribed based on Sasang constitutional medicine for Taeeumin, wasperformed.

Experimental Example 4

The measurement of lipase activity of the herbal medicinal tabletformulation for treating obesity which can be prescribed based on Sasangconstitutional medicine for Taeeumin, was measured using 4-dinitrophenylbutyrate as a substrate.

A porcine pancreatic lipase from Sigma company, USA (0.5 mg/mL), waspurchased, and was dissolved in a 0.1 mol potassium phosphate buffersolution, and then, in order to measure the lipase inhibitory efficacyof the herbal medicinal tablet formulation for treating obesity whichcan be prescribed based on Sasang constitutional medicine for Taeeumin,experiments were performed at five concentrations of 0.04%, 0.08%,0.12%, 0.16%, and 0.2%, and measured 10 times per concentration.

0.4 mL of 4-dinitrophenyl butyrate solution was added to a mixedsolution of the prepared 0.1 mL pancreatic lipase solution and 0.1 mLGambijeong M solution, and 0.1 mL of 1M Tris-HCL solution was addedthereto, and then it was reacted for 5 minutes at 37° C. in anincubator.

Then, the activity of the lipase was determined by measuring theabsorbance of 4-dinitrophenol isolated by the lipase with aspectrophotometer at 360 nm.

The experimental results were represented as relative values of thelipase to the control at 100%, and the experimental result was found tobe significant when the P value was 0.05% or less through thestatistical program SPSS, as shown in Table 9 and Table 10.

Table 9 is raw data of the lipase activity.

TABLE 9 1 2 3 4 5 6 7 8 9 10 CON 22.43334 22.18817 22.67852 22.9236922.92369 22.8011 22.8011 22.67852 22.67852 22.67852 Pan 103.2179101.1339 100.0306 99.41771 99.04995 99.90806 99.66289 99.5403 100.398499.66289 S_0.04 96.72061 101.1339 103.9534 104.5663 104.3212 102.3598102.1146 102.7276 102.605 103.4631 S_0.08 82.25559 89.61079 93.0432193.04321 90.46889 91.44959 93.53356 93.53356 91.93993 91.93993 S_0.1283.60405 80.53938 85.68802 83.84922 82.25559 83.35887 85.32025 84.5847484.9525 90.95924 S_0.16 88.50751 81.52007 80.04903 78.82317 82.1330182.86853 81.88783 82.37818 83.72663 82.50077 S_0.20 85.07508 77.4747279.31352 77.47472 76.81661 78.08765 79.19093 81.64266 85.32026 84.58474

Table 10 is a table showing the lipase activity with respect to“Gambijeong” for Taeeumin.

TABLE 10 Density Lipase activity 0.00% 100.20 ± 1.14 0.04% 102.50 ± 2.170.08%  91.05 ± 3.19 0.12%  84.51 ± 2.73 0.16%  82.44 ± 2.55 0.20%  80.48± 3.41

As shown in Table 10 and FIG. 4, the herbal medicinal tablet formulationfor treating obesity which can be prescribed based on Sasangconstitutional medicine for Taeeumin showed significant lipaseinhibitory ability from a 0.08% concentration, and it was also foundthat inhibiting lipase efficacy in the body could be utilized to lowerthe body's utilization of fat when taken with a high fat diet.

On the other hand, from the experimental results for patients whovisited the Korean clinic of the applicant, the patient's obesity (orBMI) and the usage of the composition based on the constitution could bestandardized as shown in Table 11 by using the daily content ofephedrine.

Table 11 shows the constitutional usage of the herbal medicinal tabletformulation for treating obesity which can be prescribed based on Sasangconstitutional medicine according to the embodiment of the presentinvention, wherein Gambijeong 1 to Gambijeong 4 represent the divisionby the constitution of the herbal medicinal tablet formulation fortreating obesity.

TABLE 11 Classification Ephedrine content (1 day) Usage Gambijeong 1  60-90 mg Normal weight, overweight, initial obesity Gambijeong 2 80-120 mg Overweight, obesity Gambijeong 3  90-120 mg Moderate andsevere obesity Gambijeong 4 130-140 mg Immunity, moderate, and highobesity

A manufacturing method of an herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine will now be described in detail with reference to FIG. 5 toFIG. 11. FIG. 5 illustrates a flowchart of a manufacturing method of anephedra powder agent for an herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine according to an embodiment of the present invention, and aside-effect-preventing powder agent by constitution, FIG. 6 illustratesa flowchart of a manufacturing method of an herbal medicinal tabletformulation for treating obesity which can be prescribed based on Sasangconstitutional medicine according to an embodiment of the presentinvention, FIG. 7 to FIG. 9 respectively illustrate a graph of measuringan ephedrine content every 2 hours for 10 lots in a decocting processfor 4 different ephedra with different producing districts andcollecting periods so as to manufacture an ephedra powder agent for anherbal medicinal tablet formulation for treating obesity which can beprescribed based on Sasang constitutional medicine according to anembodiment of the present invention, and FIG. 10 and FIG. 11respectively illustrate graphs for explaining a pattern relationshipbetween a Brix content and an ephedrine content in manufacturing anephedra powder agent for an herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine according to an embodiment of the present invention, by usingthe results shown in FIG. 7 to FIG. 9.

In FIG. 7 to FIG. 9, line 1 is pseudoephedrine content %, and line 2 isephedrine content %.

Generally, the herbal medicines are provided in various ways, such asdecoctions, pills, powders, granule preparations, concentrated liquidpreparations, and distillation agents, however, they are not suitable asa treatment for obesity, such as by having a peculiar smell, bittertaste, stickiness, or feeling of satiety due to excessive amounts, whichare peculiar to herbal medicine preparations, and therefore, themanufacturing method of the herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine according to the embodiment of the present invention provides atablet formulation for treating obesity that may be prescribed accordingto Sasang constitutional medicine so as to solve the above problems andachieve the obesity treatment effect without side effects according tothe prescription for each constitution based on Sasang constitutionalmedicine.

As shown in FIG. 7 and Table 12, first, the ephedrine content of ephedrawas 0.185 for spring collection in China and 0.360 for collection inPakistan, depending on the producing district and collecting period,wherein a difference between their content % was almost doubled by 0.09%and 0.18%, and thus, it can be seen that they did not reach 2.8 to 3.3%that were an amount of being able to treat obesity within 3 months.

Table 12 show data for four ephedra of different producing districts andcollecting periods.

TABLE 12 Weight of extraction liquid Extraction Extraction ExperimentalPlace of Raw Total liquid Extraction Brix time material origin Vesselmaterial weight weight rate Average Measure 6 hr S1-1 Chinese 174.7330.00 313.02 108.29 36.1% 136.40 6.4% spring S1-2 176.00 30.00 324.15118.15 39.4% 6.1% S1-3 181.65 30.00 343.16 131.51 43.8% 5.3% S1-4 189.6530.00 354.27 134.62 44.9% 5.2% S1-5 172.79 30.00 346.64 143.85 48.0%4.8% S1-6 146.20 30.00 265.85 89.65 29.9% 8.3% S1-7 174.74 30.00 369.29164.55 54.9% 4.4% S1-8 176.02 30.00 333.31 127.29 42.4% 5.6% S1-9 181.6530.00 376.73 165.08 55.0% 4.6% S1-10 189.65 30.00 400.67 181.02 60.3%4.0% S2-1 Chinese 172.80 30.00 378.30 175.50 58.5% 164.77 3.8% autumnS2-2 146.19 30.00 336.60 160.41 53.5% 4.1% S2-3 174.74 30.00 355.28150.54 50.2% 4.5% S2-4 176.01 30.00 397.11 191.10 63.7% 3.5% S2-5 181.6730.00 388.45 176.78 58.9% 3.8% S2-6 189.66 30.00 373.35 153.69 51.2%4.3% S2-7 172.87 30.00 415.24 212.37 70.8% 3.2% S2-8 146.18 30.00 317.20141.02 47.0% 4.6% S2-9 174.74 30.00 372.42 167.68 55.9% 3.9% S2-10176.00 30.00 324.61 118.61 39.5% 5.2% S3-1 Pakistan 181.64 30.00 357.51145.87 48.6% 160.64 6.0% S3-2 189.64 30.00 317.80 98.16 32.7% 8.1% S3-3172.80 30.00 299.95 97.15 32.4% 8.2% S3-4 146.19 30.00 299.02 122.8340.9% 7.0% S3-5 174.73 30.00 411.89 207.16 69.1% 4.3% S3-6 176.01 30.00415.79 209.78 69.9% 4.2% S3-7 181.66 30.00 354.54 142.88 47.6% 6.1% S3-8189.64 30.00 428.12 208.48 69.5% 4.4% S3-9 172.79 30.00 398.96 196.1765.4% 4.5% S3-10 146.18 30.00 354.08 177.90 59.3% 5.0% S4-1 Kyrgyzstan174.75 30.00 347.54 142.79 47.6% 123.90 6.2% S4-2 182.70 30.00 332.59119.89 40.0% 7.2% S4-3 168.83 30.00 290.56 91.73 30.6% 9.2% S4-4 186.9130.00 329.61 112.70 37.6% 7.7% S4-5 179.74 30.00 327.90 118.16 39.4%7.2% S4-6 146.19 30.00 326.11 149.92 50.0% 5.8% S4-7 174.73 30.00 338.70133.97 44.7% 6.3% S4-8 182.69 30.00 316.97 104.28 34.8% 7.5% S4-9 168.8230.00 320.16 121.34 40.4% 7.0% S4-10 186.90 30.00 361.13 144.23 48.1%6.1% Total alkaloid Extraction Extraction amount amount Total ExtractionPseudo Dose Total correction time Average Ephedrine Ephedrine DoseAverage correction Average 6 hr 5.5% 0.04% 0.14% 0.18% 0.15% 0.28% 0.27%0.03% 0.13% 0.16% 0.26% 0.03% 0.12% 0.15% 0.27% 0.03% 0.12% 0.15% 0.27%0.03% 0.11% 0.14% 0.27% 0.04% 0.18% 0.22% 0.31% 0.03% 0.10% 0.13% 0.29%0.03% 0.12% 0.15% 0.26% 0.02% 0.10% 0.12% 0.27% 0.02% 0.08% 0.10% 0.25%4.1% 0.04% 0.07% 0.11% 0.12% 0.27% 0.26% 0.04% 0.08% 0.12% 0.26% 0.03%0.07% 0.10% 0.20% 0.03% 0.07% 0.10% 0.28% 0.03% 0.07% 0.10% 0.24% 0.04%0.09% 0.13% 0.27% 0.03% 0.07% 0.10% 0.34% 0.05% 0.09% 0.14% 0.26% 0.04%0.08% 0.12% 0.27% 0.05% 0.10% 0.15% 0.25% 5.8% 0.04% 0.18% 0.22% 0.24%0.43% 0.53% 0.05% 0.27% 0.32% 0.48% 0.05% 0.29% 0.34% 0.50% 0.06% 0.25%0.31% 0.52% 0.03% 0.16% 0.19% 0.61% 0.03% 0.15% 0.18% 0.60% 0.04% 0.22%0.26% 0.50% 0.04% 0.15% 0.19% 0.62% 0.03% 0.15% 0.18% 0.52% 0.03% 0.17%0.20% 0.49% 7.0% 0.02% 0.19% 0.22% 0.24% 0.42% 0.41% 0.03% 0.22% 0.32%0.53% 0.04% 0.26% 0.34% 0.49% 0.03% 0.23% 0.31% 0.50% 0.03% 0.22% 0.19%0.31% 0.02% 0.17% 0.18% 0.36% 0.02% 0.20% 0.26% 0.47% 0.03% 0.23% 0.19%0.29% 0.03% 0.21% 0.18% 0.30% 0.02% 0.19% 0.20% 0.39%

Therefore, it is necessary to concentrate and quantify the activeingredient in order to extract ephedrine, which is an active ingredientof the herbal medicinal tablet formulation for treating obesity whichcan be prescribed based on Sasang constitutional medicine according tothe embodiment of the present invention, only from the natural componentephedra.

Here, the quantifying is for maintaining the ephedrine content ofephedra powder at a predetermined value, and a sugar measure, Brix, isused. Brix is precisely called Brix %, and this unit is an amount ofsolute dissolved in an aqueous solution as a unit of %, and it is a“soluble solid”, which means that a high Brix is high in a solublesolid, including salt, protein, acid, and the like as well as a sugarcontent, and it can be used as a measure of the ratio of ephedrinecontent by measuring very widely used Brix.

To this end, the method for manufacturing the ephedra powder agent andside-effect-preventing powder agent for each constitution for the herbalmedicinal tablet formulation for treating obesity which can beprescribed based on Sasang constitutional medicine according to theembodiment of the present invention includes: small-dividing each of theephedra for ephedra powder and the herbal ingredients prescribed for theside-effect-preventing powder agent for each constitution shown in Table2, based on the weight per pack (S10); and primarily concentrating andquantifying ephedrine, which is an active ingredient, through the Brixmeasurement while undergoing a hydraulic decocting process (S20).

The hydraulic decocting process, which is a process of facilitating thedecocting by applying hydraulic pressure, generally includes: afterwashing with water, immersing in water at a temperature of 10 to 20° C.,about 10 times for each weight, for 15 to 20 hours, to increaseextraction of the active ingredient (S21); and then boiling eachmaterial at a temperature of 95 to 100° C. for 4 to 5 hours to extractan extract liquid having a high yield (S21); measuring Brix everyheating time (S23); checking whether the extract liquid has 7 Brix ormore (S24); when the Brix of the extract liquid is not more than 7 Brix,the heating time is increased, while when the Brix of the extract liquidis more than 7 Brix, filtering foreign materials using a nanofilter of100 mesh (S25); and maintaining cooling at 40 to 50° C. to preventmicroorganisms and storing it while stirring it to prevent precipitationof solids (S26).

In the method for manufacturing the ephedra powder agent andside-effect-preventing powder agent for each constitution for the herbalmedicinal tablet formulation for treating obesity which can beprescribed based on Sasang constitutional medicine according to theembodiment of the present invention, the reason for primarilyquantifying the ephedrine to 7 Brix or more using the hydraulicdecocting process was that the Brix substantially increased with theheating time of the hydraulic decocting process as shown in FIGS. 10 and11, but the ephedrine content of ephedra remained constant atapproximately 7 Brix even if the producing districts and collectingperiods of the ephedra were different, or it had a pattern of decreasingby pressure or temperature, thus there was no need to use unnecessaryenergy in a situation in which the yield of the active ingredient waskept constant.

Experimental Example 5

The Brix measurement in the hydraulic decocting process and the contentmeasurement of ephedrine in each Brix value were performed as follows.

For four ephedra (by country of origin-made in China, Pakistan,Kyrgyzstan/by collecting period-Chinese spring and autumn harvest),namely S1 (Chinese, spring), S2 (Chinese, autumn), S3 (Pakistan), and S4(Kyrgyzstan), the same specimen was divided into 10 batches and tested;the extraction conditions were 10 times the weight of the test material,and after heating, the extract was made every 2 hours from the point of100° C.; the weight of each extract was calculated by weight (extractweight=total weight-container weight-raw material weight); the Brixvalue for each lot was measured using a Brix densitometer called aRefractometer, ATAGO PAL-1; and the total alkaloid and ephedrinecontents were measured using HPLC and Shimadzu 20-A series.

[Quantity Test]

Measured as a total alkaloid [ephedrine (C₁₀H₁₅NO: 165.23 g/mol) andpseudoephedrine (C₁₀H₁₅NO: 165.23 g/mol)], standard solution: ephedrinehydrochloride (dried at 105° C. for 3 hours in advance), approximately50 mg of the standard product is precisely weighed, and diluted methanol(1→2) is added thereto to make exactly 20 mL. 2 mL of this solution isaccurately taken, and diluted methanol (1→2) is added thereto to makeexactly 100 mL.

Test solution: About 5 mL of the extract is precisely weighed, put it ina stoppered centrifuge tube, and 20 mL of diluted methanol (1→2) isadded thereto and shaken for 30 minutes, and then is centrifuged to takethe supernatant.

Next, in order to maintain each material at a predeterminedconcentration, it is boiled at a temperature of 95 to 100° C. andextracted until the concentration reached 7 to 10 Brix for secondaryquantification. 20 mL of methanol (1→2) diluted in the residue is againused, and the above operation is repeated twice. All the extracts arecombined, and the diluted methanol (1→2) is added thereto to makeexactly 100 mL.

Detector: UV absorbing photometer (measurement wavelength 210 nm)

Column: a stainless steel pipe having an inner diameter of 4-6 mm and alength of 15-20 cm is filled with 5-10 μm octadecylsilyl silica gel forliquid chromatography.

Constant temperature around 45° C.

Mobile phase: sodium lauryl sulfate solution(1→128)*acetonitrile*phosphate mixture (640:360:1)

The results are shown in Table 13 and Table 14.

TABLE 13 Brix (% Brix) 2 h 4 h 6 h China (spring) 3.30 4.30 5.50 China3.00 3.80 4.10 (autumn) Pakistan 4.10 5.10 5.80 Kyrgyzstan 3.60 5.307.00

TABLE 14 Total alkaloid (%) 2 h 4 h 6 h China (spring) 0.28 0.26 0.27China (autumn) 0.32 0.26 0.26 Pakistan 0.55 0.67 0.53 Kyrgyzstan 0.440.46 0.41

As can be seen from Table 13 and Table 14, according to the hydraulicdecocting process, it is about 0.41% on average at 7 Brix, and thecontent of ephedrine is insufficient to make 3 to 4% of the ephedrinepowder agent, and in the case of continuous heating, destruction ofactive ingredients such as ephedrine occurs, and thus, secondaryephedrine concentration extraction and quantification is performed usinga vacuum low-temperature concentration process (S30).

In order to again concentrate the extract extracted in the hydraulicdecocting process at a high concentration while lowering the heatingtemperature and increasing the concentration rate under reduced pressureand in a vacuum, under reduced pressure conditions, the extract isvacuum-reduced and concentrated for 5 to 6 hours under the reducedpressure condition of 08 to 09 bar and the concentration temperature of50° C. to 55° C.

Meanwhile, even in this case, the concentration is also maintainedconstant using the Brix, and while confirming whether the concentrationof each material becomes approximately 30 to 35 Brix, it is secondarilyquantified to prepare a concentrate.

Here, in order to increase and maintain the ephedrine content %, it isdetermined using a Brix densitometer whether the concentration of theephedra concentrate is 30 to 35 Brix, and the reason is that, as shownin Table 15, the total alkaloid correction average content % alsoincreases with an increase in the Brix according to a vacuumdecompression container, but thereafter, in lyophilization, crystals aregenerated in the case of 10 to 20 Brix, or the ephedrine content israther lowered under the influence of temperature and pressure in thecase of 40 Brix or more.

In addition, it was also possible to concentrate it up to 30 Brixthrough the hydraulic decocting process, but in this case, as describedabove, the content of ephedrine was reduced by heat, and theconcentration time was increased by 2 to 3 times or more.

Table 15 is a table summarizing problems that occur when the Brixincreases through a hydraulic decocting process.

TABLE 15 10 Brix 20 Brix 30 Brix 40 Brix 50 Brix Total 1.1% 1.9% 2.8%3.5% 5% alkaloid correction average content % Problem Crystal CrystalClose to Ephedrine Ephedrine generation generation effective contentcontent during during ephedrine reduction reduction lyophilizationlyophilization content (temperature, (temperature, pressure effect)pressure effect)

The ephedrine is secondarily concentrated and quantified by the vacuumlow-temperature concentration process, and the averaged concentrate islyophilized (freeze-dried) by mixing different concentrates for each lotand each batch (S40). The lyophilization is a drying method that removesmoisture using the property of sublimating only the moisture in thesample when the sample is frozen and then reduced in pressure, andaccording to the lyophilization, compared to simple hot air drying, winddrying, or high temperature drying, the dried material contains a myriadof gaps, so it is easy to absorb moisture, so it is easy to rehydratequickly and completely.

Therefore, the herbal medicinal tablet formulation for treating obesitywhich can be prescribed based on Sasang constitutional medicineaccording to the embodiment of the present invention has the effect ofbeing disintegrated within 30 minutes when taken with water.

Meanwhile, the ephedra concentrate concentrated at 30 to 35 Brix mayalso drop the ephedrine content %, which is the active ingredient of theephedra concentrate, according to the freezing temperature and freezingtime, and thus, after performing an experiment to find a suitablefreezing temperature and time, the ephedrine content % was measured toconfirm whether it was reduced.

The concentrate of the secondary quantified concentrated at 2.8%ephedrine content was divided into 3000 ml trays of a lyophilizer, andthe temperature and freezing time were varied to measure the ephedrinecontent % and shown in Table 16.

Table 16 is a table showing a change in ephedrine content % according toa freezing temperature and a time.

TABLE 16 Temperature (° C.) −0 to −10° C. −10 to −20° C. −20 to −30° C.−30 to −40° C. −40 to −50° C. −50 to −60° C. Time (h) 18 hours 14 hours10 hours 8 hours 5 hours 3 hours Total alkaloid correction 2.8% 2.78%2.77% 2.8% 2.5% 2.41% average content

As a result of the test, it is determined that the freezing time at atemperature of −40 to −50° C. is suitable in terms of a time of 3 to 5hours, but it is suitable to freeze it at −30 to −40° C. for 8 hours,which may be maintained within the error range even if it takes a longtime to maintain the total alkaloid corrected average content %, thatis, ephedrine content %.

Subsequently, drying proceeds, and at this time, in order to preservethe ephedrine content % well, the experiment results are shown in Table17 while varying the drying temperature, pressure, and time.

Table 17 shows a change in ephedrine content % according to a dryingcondition.

TABLE 17 Item 01 02 03 04 05 06 07 Temperature (° C.) −30 −20 −10 0 1020 30 Pressure (mb) 50 50 50 5 5 0 0 Time (h) 12 hours 18 hours 24 hours28 hours 32 hours 48 hours 60 hours Total alkaloid correction 2.31%2.50% 2.52% 2.55% 2.56% 2.6% 2.81% average content

As can be seen from Table 17, when the lyophilization was performedunder the freezing condition at a temperature of −30 to −40° C. and afreezing time of 8 hours and the drying condition at a temperature of 30to 40° C. and a freezing time of at least 60 hours, the activeingredient of the concentrated liquid was well preserved, and a highconcentration and yield of the ephedra powder agent was obtained.

The lyophilized phase dried in the lyophilization process (S40) waspulverized to make a powder of a 40 to 45 mesh size, and then screenedwith a sieve of 40 to 45 mesh to screen the pulverized powder medicineto a certain size (S50).

The ephedrine content of the ephedra powder agent, which was a powdermedicine of a predetermined size, prepared as described above, wasmeasured (S60), and then predetermined amounts of the ephedra powderagent and the herbal medicine powder agent for eachside-effect-preventing powder agent were hermetically packaged in bags(S70).

A manufacturing method of the herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine according to the embodiment of the present invention will nowbe described in detail with reference to FIG. 6.

In the manufacturing method of the herbal medicinal tablet formulationfor treating obesity which can be prescribed based on Sasangconstitutional medicine according to the embodiment of the presentinvention, the ephedra powder agent and the side-effect-preventingpowder agent for each constitution are measured and mixed depending onthe ephedrine content of the ephedra powder agent (S110).

In this case, the prescription is checked by referring to a list of thepatient's weight, obesity, constitution based on Sasang constitutionalmedicine, side effects, and the like (S120), and when it is necessary tocorrect the prescription, the amount of the side-effect-preventingpowder agent for each constitution with respect to the amount of theephedra powder agent or the weight of the ephedra powder agent iscorrected within the range of 8-10:1 to 9-11:1 (S121).

When the checking and correcting of the prescription are not requiredwith reference to the list of the patient's weight, obesity,constitution based on Sasang constitutional medicine, side effects, andthe like, in order to prepare tablet formulations such as croscarmellosesodium, microcrystalline cellulose, and magnesium stearate, which act asdisintegrants or hardness agents, the subsidiary material is mixed andput into the tableting apparatus, and then as shown in FIG. 1, it istableted to have a size having a thickness of 590±010 mm, a diameter of176±020 mm, and a weight of 646 mg±50% (S130).

After the tableting process (S130), in order to prevent the activeingredient from being destroyed when exposed to air, it is coated byinstalling the coating liquid in the fixed frame of the injector,opening the liquid adjustment nozzle of each injector, increasing thepressure of the liquid pump to 1 to 2 bar, letting the initial liquidflow for 3 minutes, and then adjusting the pressure and the amount ofair in the liquid pump (S140).

The coating condition is a 60-250 ml/min liquid volume at a speed of 2-7rpm at a pressure of 5˜6 kg/cm² with a 12 Fmm nozzle size.

It is coated with the coating solution and then cooled and dried at25-30° C. for 20 minutes at a low speed; defective products are takenoff, and the pills are packed in containers accommodating 90 tablets soas to be able to be taken three times a day for three months; and alabel on which patient, constitution, ephedrine content %, andprescription information for each constitution is recorded is attachedto the container.

Experimental Example 6

To confirm that the herbal medicinal tablet formulation for treatingobesity manufactured by the manufacturing method of the herbal medicinaltablet formulation for treating obesity which can be prescribed based onSasang Medicine according to an embodiment of the present invention waseffective in reducing obesity, 93 subjects were dosed for 10 days or 5days, respectively, and the appetite suppressing effect, conveniencewhen taking it, absorption rate, and preference were checked.

Although the content of the herbal medicine for each constitution wasdifferent, when confirming the results for the present invention, therewas no variation for each constitution.

Experiment Method

(1) After 3 months of taking it, 4 kinds of appetite suppression effectssuch as “none, normal, existence, and very good” were confirmed.

(2) In order to check the convenience when taking it, the conveniencedegree as 4 kinds of “none, normal, existence, and very good” wasconfirmed from those who have taken the existing herbal decoction orcapsule.

(3) In order to check the absorption rate, the convenience degree as 4kinds of “none, normal, existence, and very good” was confirmed fromthose who have taken the existing herbal decoction or capsule.

(4) In order to check the overall preference, 4 preferences of “none,normal, existence, and very good” was confirmed from those who havetaken the existing herbal decoction or capsule.

Since the composition of the herbal medicinal tablet formulation(Gambijeong) for treating obesity which can be prescribed based onSasang constitutional medicine according to the embodiment of thepresent invention mainly reduces body fat, it is first checked throughexperiments whether it has the clinical effectiveness of weight loss forSasang constitution, whether the Gambitang composition as a decoctionmedicine is stable for Taeeumin, and whether there is a clinical effectof weight loss without side effects.

Table 18 shows an experimental result of a clinical effect of Gambijeongon Taeeumin.

TABLE 18 Appetite suppression Absorption effect Convenience ratePreference Very good 39 64 51 50 Existence 30 39 38 27 Normal 19 0 3 5None 5 0 1 1 Total 93 93 93 93

As can be seen in Table 18, the appetite suppression effect was found tobe effective in 69 (74%) out of 93 patients; the convenience was foundto be effective in 93 (100%) out of 93 patients; the absorption rate,which was improved compared to that of the existing decoction orcapsule, was found to be effective in 89 (95%) out of 93 patients; andthe overall preference was found to be effective in 77 (82%) out of 93patients. It was confirmed that the herbal medicinal tablet formulationand manufacturing method for treating obesity which can be prescribedbased on Sasang Medicine according to the embodiment of the presentinvention were more convenient, preferred, and improved in absorptionrate compared to other methods of taking the traditional herbalmedicine, and it was confirmed that the herbal medicine according toExample 6 had the appetite suppression effect.

INDUSTRIAL APPLICABILITY

The herbal medicinal tablet formulation and manufacturing method fortreating obesity which can be prescribed based on Sasang Medicineaccording to the embodiment of the present invention, since it isadvantageous in that the herbal medicine varies in the content of thedrug according to the constitution and the degree of the disease, evenfor the same disease, and thus the prescription varies, may provide theadvantage of the herbal medicine, and may provide convenience andeffective effects to a person taking it by increasing and quantifyingthe yield of the active ingredient.

In addition, the herbal medicinal tablet formulation and manufacturingmethod for treating obesity which can be prescribed based on SasangMedicine according to the embodiment of the present invention mayprovide an herbal medicine with low stability to be more convenient totake and to be quickly absorbed.

While this invention has been described in connection with what ispresently considered to be practical exemplary embodiments, it is to beunderstood that the invention is not limited to the disclosedembodiments.

1. An herbal medicinal tablet formulation for treating obesity which canbe prescribed based on Sasang constitutional medicine, comprising: anephedra powder agent of which ephedrine content is concentrated to be3.0 to 4.0%, which is greater than 0.5 to 2.5% when it is in a naturalstate, and of which the ephedrine content is maintained constant at 3.0to 4.0%; and a side-effect-preventing powder agent for each constitutionprescribed based on Sasang constitutional medicine in order to prevent aside effect of the ephedra powder agent, wherein a weight ratio of theephedra powder agent and the side-effect-preventing powder agent is8-10:1 to 9-11:1.
 2. The herbal medicinal tablet formulation fortreating obesity which can be prescribed based on Sasang constitutionalmedicine of claim 1, wherein the side-effect preventing powder agent foreach constitution includes alisma 1, platycodon 1, puerariae 1, acorusgramineus1, castanea mollissima 2, coicis semen 2, raphani semen 1,armeniacae amarum semen 1, cinnamon-vine 2, and nelumbinis semen 2 withrespect to the ephedra powder agent 1 as a weight ratio in a case ofTaeeumin.
 3. The herbal medicinal tablet formulation for treatingobesity which can be prescribed based on Sasang constitutional medicineof claim 1, wherein the side-effect preventing powder agent for eachconstitution includes talcum 2, plaster 1, peppermint 1, gardeniaefructus 1, schizonepeta 1, rhubarb 1, natrii sulfas 1, rehmanniae radixcervi 2, and moutan 1 with respect to the ephedra powder agent 1 as aweight ratio in a case of Soyangin.
 4. The herbal medicinal tabletformulation for treating obesity which can be prescribed based on Sasangconstitutional medicine of claim 1, wherein the side-effect preventingpowder agent for each constitution includes ginseng radix 1, astragaliradix 2, atractylodis macrocephalae rhioma 1, cinnamon 1, ginger 1,poria cocos 1, zizyphi fructus1, hawthorn 1, citrus unshiu markovich 1,and magnoliae cortex 1 with respect to the ephedra powder agent 1 as aweight ratio in a case of Soeumin.
 5. The herbal medicinal tabletformulation for treating obesity which can be prescribed based on Sasangconstitutional medicine of claim 1, wherein when an ephedrine content isconstant at 3 to 4%, a weight of the ephedra powder agent is preferablyabout 360 g for Taeeumin, 297 g for Soeumin, and about 360 g forSoyangin.
 6. The herbal medicinal tablet formulation for treatingobesity which can be prescribed based on Sasang constitutional medicineof claim 5, wherein a weight ratio of the side-effect-preventing powderagent for each constitution with respect to the ephedra powder agent ispreferably about 8-10:1 in Taeeumin, 9-11:1 in Soeumin, and 8-10:1 inSoyangin.
 7. The herbal medicinal tablet formulation for treatingobesity which can be prescribed based on Sasang constitutional medicineof claim 1, wherein the ephedra powder agent is primarily concentratedand quantified at 6 to 8 Brix through a hydraulic decocting process, andthen concentrated and quantified at 30 to 35 Brix through alow-temperature vacuum concentrating process and then lyophilized.